: The proposed research will examine mechanisms of CNS white matter injury following anoxia- ischemia, which is of causal relevance to periventricular leukomalacia (PL), the most common neurological lesion associated with cerebral palsy. Whole white matter structures from perinatal rats will be subjected to anoxic-aglycemic insults in vitro under conditions that allow fluorescent imaging of intracellular free Ca and membrane integrity. Stated Aims are: to develop an appropriate model; to develop techniques for in situ measurements of Ca and membrane integrity; to use these methods to determine the responses to anoxic-aglycemic insults; to assess the importance of Ca influx versus release from intracellular stores; to assess the relative importance of voltage-gated Ca channels, ligand-gated Ca channels and Na/Ca exchange in mediating the observed changes; to assess the role of extracellular K and glutamate in these processes; and to apply the results of these experiments to the functional loss experienced by CNS white matter during anoxia-ischemia.